Apparatus and method for liquid sample introduction

ABSTRACT

A method and apparatus for introducing droplets of liquid sample into an analysis device using a gas stream, the droplets being produced by the application of acoustic energy to a quantity of liquid sample. Acoustic energy may be applied to a quantity of liquid sample located on a solid surface of a sample support so as to eject a droplet of sample from the quantity of sample; the droplet of sample may be entrained in a gas stream; and the droplet of sample may be transported into the analysis device using the gas stream.

FIELD OF THE INVENTION

This invention relates to the field of liquid sample introductionsystems for analytical instruments and relates to those analysis devicesfor which sample must be introduced in the form of a stream of droplets.The invention relates to a means for utilizing an acoustic dropletgenerator for producing droplets for direct injection into an analysisdevice.

BACKGROUND

Liquid sample supplied to an analysis device in the form of droplets isusually provided using a nebulizer to generate an aerosol. Analysisdevices which utilize such droplets include ionization and/or excitationsources such as microwave induced plasma (MIP), inductively coupledplasma (ICP) and flames. The analysis devices provide spectrometerswhich perform MIP and ICP optical emission spectrometry (OES), MIP andICP mass spectrometry (MS), atomic absorption spectrometry (AA) andatomic fluorescence spectroscopy (AFS). Typically the sample-containingliquid is formed into a stream of droplets using a nebulizer utilizing astream of inert gas such as argon. Nebulizers produce droplets with awide range of sizes. However where the analysis device utilizes a plasmaor flame to dissociate and excite or ionize the sample, as both plasmasand flames are inefficient at dissociating large droplets, a spraychamber is usually placed between the nebulizer and the torch so as toexclude large droplets from the sample stream entering the analysisdevice. The spray chamber filters the stream of droplets by causing theflow to follow a tortuous path such that the larger droplets impingeupon surfaces in the spray chamber and are drained away, smallerdroplets being carried by the flow of gas into the torch. In the casesof ICP-OES and ICP-MS it is well known that only 1-2% of the nebulizedsample-containing liquid is in the form of sufficiently small dropletssuitable for processing within the torch, and that this form of sampleintroduction is therefore inefficient.

Alternative methods of producing a stream of sample droplets include theuse of continuous fluid jet micro-droplet generator (G. M. Hieftje andH. V. Malmastadt, Analytical Chemistry, Vol. 40, pp. 1860-1867, 1968)and vibrating orifice monodisperse aerosol generator (H. Kawaguchi etal., Spectrochimica Acta, vol. 41 B, pp. 1277-1286, 1986, T. Nomizu etal., Journal of Analytical Atomic Spectrometry, vol. 17, pp. 592-595,2002), The ability to produce droplets one at a time and thereby morecompletely control the droplet ejection process—so-called“droplet-on-demand” techniques—have long been seen as desirable. Wherethe droplet generator is of a type in which the droplet generationapparatus enables a single droplet to be ejected in response to acontrol signal, the droplet generator is one of a class of generatorstermed droplet-on-demand generators. An early generator with thiscapability designed principally for inkjet printing was apiezoelectrical droplet generator (U.S. Pat. No. 3,683,212). Such adroplet generator was employed to create a stream of droplets containingsample material, the droplets being passed through an oven so as to makethe droplet evaporate to complete or partial dryness before injectioninto an ICP in order to study oxide ion formation (J. B. French, B.Etkin, R. Jong, Analytical Chemistry, Vol. 66, pp. 685-691, 1994). Thiscoupling of the piezoelectric droplet generator and oven was termed themonodisperse dried microparticulate injector (MDMI) and such systemshave been used in other studies (J. W. Olesik and S. E. Hobbs,Analytical Chemistry, vol. 66, pp. 3371-3378, 1994; A. C. Lazar and P.B. Farnsworth, Applied Spectroscopy, vol. 53, pp. 457-470, 1999; A. C.Lazar and P. B. Farnsworth, Applied Spectroscopy, vol. 51, pp. 617-624,1997). Use of the piezoelectric droplet generator without thedesolvation in an oven has been successfully implemented as asub-nanolitre sample introduction technique for Laser-Induced BreakdownSpectroscopy and Inductively Coupled Plasma Spectrometry (S. Groh etal., Analytical Chemistry, vol. 82, pp. 2568-2573, 2010; A. Murtazin etal., Spectrochimica Acta, vol. 67B, pp. 3-16, 2012).

All these droplet generation devices require liquid sample to be fedinto an enclosed volume within the droplet generation device. Typicallysample is prepared and stored in vessels, and the vessels are usuallystored in an array close to the analysis device, so that the vessels maybe accessed by an autosampler. The autosampler positions a take-up tubewithin one of the vessels, and sample is drawn into the tube andtransported into the droplet generator using suction. Hence thesample-containing liquid comes in contact with the take-up tubing andwith the internal surfaces of the droplet generator. Once the sampletake-up is complete, the autosampler withdraws the take-up tubing fromthe sample-containing vessel and moves it to a vessel containing washsolution. Wash solution is drawn into the take-up tubing and into thedroplet generator and flushed to waste in order to wash out the remainsof the previous sample before the next sample is admitted. For all thedroplet generation devices described above, whether or not anautosampler is utilized, means such as tubing to transfersample-containing liquid from a storage vessel is required and thedroplet generator itself presents exposed surfaces to thesample-containing liquid.

Due to the increasingly routine use of spectrometry, sample throughputhas become one of the most important requirements as often it is thiswhich ultimately determines the cost-per-analysis in routineapplications. With the increased sensitivity of instrumentation andautomated sample handling, sample throughput is largely limited not bythe sample introduction or analysis time but rather by memory effectscaused by deposition of material from the previous sample on componentsof the sample introduction system and spectrometer. Due to the increasedsensitivity of the spectrometers and their ultimate detection limits,material deposited upon the sample introduction system is graduallywashed away during the “wash” cycle described above, and typically atleast 40-60 seconds is needed after each sample to reduce memory effectsbelow an acceptable threshold. In addition, the time to transport liquidfrom a containment vessel to the droplet generator may be significant,adding time both for sample uptake and wash solution uptake.

Development of instrumentation has increased the sensitivity of analysisdevices and frequently sample solutions require dilution. Variousmethods for automatic dilution of samples have been devised (asdescribed for example in U.S. Pat. No. 7,998,434). In order to monitorand correct for variations in accuracy, internal standards are oftenused. Both dilution and addition of standards requires the mixing ofliquids prior to introduction to the analysis device. With all thedroplet generation devices above, typically the liquids to be mixed areeither mixed within a vessel prior to take-up, or are mixed at alocation between the vessels containing the liquids and the dropletgenerator. As such, additional liquid handling devices or process stepsare required, and additional vessels or separate mixing devices arerequired. Any mixing devices and associated liquid containment conduitsmust also be washed out prior to their next use.

Acoustic droplet ejection systems have been developed utilising aphenomenon first reported by R. W. Wood and A. Loomis in 1927[Philiosophical Magazine, 4 (22), 417-436]. Acoustic energy emitted froma transducer can be converted to kinetic energy in a liquid. If acousticenergy is focused near a free surface of the liquid, droplets may beejected from the surface of the liquid, the droplet size scalinginversely with the frequency of the acoustic energy. Droplet volumesfrom ˜20 pl to 2 μl and droplet ejection rates of hundreds of dropletsper second may be produced. Unlike other droplet ejection devices, nocontact between the sample liquid and the droplet ejector or samplingapparatus such as nozzles, pipette tips or pin tools occurs. Prior artacoustic droplet ejectors have been used to eject droplets upwards fromwell plates to be deposited onto solid surfaces or receiving plateslocated immediately above the well plates. Hence droplets aretransferred from containment vessels onto receiving vessels inrelatively close proximity.

SUMMARY OF THE INVENTION

In light of the above, the present invention has been made.

In a first independent aspect, the present invention provides a methodof introducing liquid sample into an analysis device comprising thesteps of: applying acoustic energy to a quantity of liquid samplelocated on a solid surface of a sample support so as to eject a dropletof sample from the quantity of sample; entraining the droplet of samplein a gas stream; and transporting the droplet of sample into theanalysis device using the gas stream.

In a further independent aspect, the present invention provides a sampleintroduction system for an analysis device comprising: a solid surfaceof a sample support suitable for locating a quantity of liquid sample;an acoustic transducer arranged so that, in use, acoustic energy isemitted towards the solid surface; a gas supply arranged to supply astream of gas; and a gas conduit arranged between the gas supply and thesample support and between the sample support and an inlet of theanalysis device.

In use, a quantity of liquid sample is located on a solid surface andacoustic energy from an acoustic transducer is directed towards theliquid sample. The acoustic energy causes a droplet of liquid sample tobe ejected from a free surface of the quantity of liquid sample. A gasstream is directed so as to entrain the droplet of sample and transportthe droplet away from the quantity of liquid sample on the solid surfaceand into an analysis device. Means for directing the gas stream so as toentrain the droplet of sample and preferably transport it so that itdoes not come into contact with any surfaces along a transport pathbetween the quantity of liquid sample and the analysis device are hereindescribed.

Preferably the droplet of sample is transported into the analysis devicealong a transport path and the droplet of sample does not contact anysolid surface along the transport path after leaving the quantity ofsample and before entering the analysis device. Preferably gas streamenters the analysis device as it enters a sample inlet. Preferably thedroplet of sample entrained in the gas stream enters the analysis deviceand sample material within the entrained droplet of sample is excited orionized within the analysis device without having come into contact withany solid surface on its journey from the quantity of sample.

In some embodiments the quantity of sample is located on the solidsurface of a sample support within a containment vessel, preferably thecontainment vessel is one of an array of containment vessels, the samplesupport comprising the array of containment vessels; more preferably thequantity of sample is located on the solid surface of a sample supportwithin a well plate. Preferably the sample support comprises a pluralityof sample support sites, such as containment vessels, indentations,protuberances, or sites having undergone surface treatment such asetching or impregnation. In some embodiments the quantity of sample islocated on the solid surface of a sample support in the form of a liquiddrop, in which case the sample support may not comprise a containmentvessel, but may be, for example, a flat glass slide or a local surfaceprotuberance or other localized site.

The solid surface preferably comprises an inert material; preferably theinert material comprises one or more of: polystyrene, PFA, LCP, PTFE,Nylon, PEEK, ceramic or glass.

Preferably the acoustic energy is applied to the quantity of samplethrough the solid surface of the sample support. Preferably the acoustictransducer is arranged so that, in use, acoustic energy is emittedtowards a first surface of the sample support and the quantity of liquidsample is located upon a second surface of the sample support, thesecond surface being different from the first surface. In someembodiments the acoustic transducer is arranged to emit acoustic energythrough a side wall of a containment vessel, and the quantity of sampleis located within the containment vessel. Preferably the first andsecond surfaces of the sample support are substantially parallel to oneanother. Preferably, in embodiments in which the sample supportcomprises a containment vessel, the first surface is arranged, in use,to be a downward side of the sample support and the second surface isarranged to be an upward side of the sample support; most preferably thesecond surface is inside the containment vessel and is the inside lowersurface of the containment vessel. Where the sample support comprises aflat plate, and the quantity of sample is located upon one side of theflat plate (the second surface), the first surface is arranged, in use,to be the other side of the sample support.

A gas supply is arranged to supply a stream of gas. The gas streampreferably comprises inert gas. More preferably the gas substantiallyonly comprises inert gas. Preferably the gas comprises one or more of:N₂, He, Ar, SF₆, Xe, Ne, Kr. The gas flow rate is preferably between 0.1and 3 l·min⁻¹ at a pressure between 0.1 and 2 bar. The gas may be at anysuitable temperature, lower temperatures being beneficial where theliquid sample comprises volatile substances. Preferably a flow of inertgas is directed at the quantity of sample on the solid surfaceimmediately prior to applying the acoustic energy to the quantity ofsample.

In other embodiments, such as those in which the analysis device is anatomic absorption spectrometer, the gas is preferably a pre-mixedmixture of the desired oxidant and fuel gases in the appropriate ratios,or is one of the desired oxidant and the desired fuel gas.

In some preferred embodiments a gas stream is supplied at a first flowrate whilst transporting the droplet of sample, and a gas stream issupplied at a second flow rate when not transporting a droplet of sampleand immediately prior to applying the acoustic energy to the quantity ofsample, the second flow rate preferably being greater than the firstflow rate. The first flow rate may be greater than the second flow ratein some embodiments, but preferably the second flow rate is greater thanthe first flow rate. The application of the second flow rate gas streamadvantageously purges the volume in the region around the quantity ofsample of residual gases prior to droplet ejection. Droplet ejection isinitiated by the application of a first magnitude of acoustic energy.Whilst this purging is being performed a second magnitude of acousticenergy may be applied, the second magnitude being lower than the firstmagnitude, so as to determine properties of the quantity of sample, suchas, for example, the distance between the acoustic transducer and thefree surface of the quantity of sample, which is of use for adjustmentof the focus of the acoustic energy subsequently applied. Hencepreferably the gas stream is supplied at a first flow rate whilsttransporting the droplet of sample, and the gas stream is supplied at asecond flow rate when not transporting a droplet of sample and whilst asecond magnitude of acoustic energy is being applied to determine theproperties of the quantity of sample immediately prior to applying afirst magnitude of acoustic energy that results in droplets beingejected from the quantity of sample, the second flow rate being greaterthan the first flow rate.

Preferably the gas stream is supplied so as to form a gas curtain whichat least partially surrounds the quantity of sample and/or partiallysurrounds the droplet of sample as it leaves the surface of the quantityof sample, the term gas curtain being herein used to mean a partial orcomplete sheath of gas. Apparatus embodying the invention comprises agas conduit arranged between the gas supply and the sample support andbetween the sample support and an inlet of the analysis device.Preferably the gas conduit comprises a first gas conduit arrangedbetween the gas supply and the sample support and a second gas conduitarranged between the sample support and an inlet of the analysis device.Where the quantity of sample is located on the solid surface of thesample support in the form of a liquid drop, preferably the first gasconduit is configured to provide gas to the first surface of the samplesupport, and the gas stream passes through a portion of the samplesupport in one or more channels, the channels extending from the firstsurface through to the second surface of the sample support, thequantity of sample being located upon the second surface of the samplesupport (the first and second surfaces of the sample support having beendescribed above). In a preferred embodiment where the quantity of sampleis located on the solid surface of the sample support within acontainment vessel and the second side of the sample support is insidethe containment vessel and is the inside lower surface of thecontainment vessel, preferably the gas stream passes through a portionof the sample support in one or more channels. In some embodiments, thechannels extend from the first surface and within one or more side wallsof the containment vessel to a third surface, the third surface being agreater distance from the first surface than the is the quantity ofsample, e.g. the third surface may form the rim of the containmentvessel. In other embodiments, the channels pass into the sample supportthrough a surface and extend within the sample support to the thirdsurface. Where the containment vessel is a well within a well plate, thethird surface is preferably part of the upper surface of the well plate,as will be further described. Where a gas curtain at least partiallysurrounds the quantity of sample and the quantity of sample is locatedon an inside lower surface of a containment vessel, the gas curtainpartially surrounds the quantity of sample whilst the gas travels withinone or more channels formed within one or more side walls of thecontainment vessel. Preferably the curtain of gas is primarily directednormal to and away from the side of the solid surface upon which thequantity of sample is located. Preferably the gas conduit supplies thestream of gas in the form of a gas curtain at least partiallysurrounding a volume adjacent the sample support site so as to partiallysurround the droplet of sample as it leaves the surface of the quantityof sample on the sample support site.

In preferred embodiments the acoustic transducer applies acoustic energyto the quantity of sample through the solid surface of the samplesupport. Preferably the acoustic transducer applies acoustic energy tothe quantity of sample through the first surface of the sample supportand out of the second surface of the sample support, the first andsecond surfaces having being described above. It is preferable that atleast a portion of the first and second surfaces are substantiallyparallel so that the path length through the sample support along thepath of the acoustic energy is substantially the same for all beams ofacoustic energy. In one preferred embodiment the acoustic transducer islocated within the first gas conduit, as will be further described.

Apparatus embodying the invention comprises a gas conduit arrangedbetween the gas supply and the sample support and between the samplesupport and an inlet of the analysis device. Preferably the gas conduitcomprises a first gas conduit arranged between the gas supply and thesample support and a second gas conduit arranged between the samplesupport and an inlet of the analysis device. Preferably the second gasconduit comprises a carrier tube and the carrier tube accepts at leastsome of the gas which is, in use, delivered by the first conduit. Morepreferably the carrier tube accepts substantially all the gas which is,in use, delivered by the first conduit. The gas conduit serves to atleast partially constrain the gas stream as it travels from the samplesupport to the analysis device, and thereby constrain part or the entiretransport path of the ejected droplet. In preferred embodiments, thesecond gas conduit comprising the carrier tube serves to at leastpartially constrain the gas stream as it travels from the sample supportto the analysis device, and thereby constrain part or the entiretransport path of the ejected droplet.

In preferred embodiments the first gas conduit is sealed to a surface ofthe sample support with a gas-tight seal, so as to surround the one ormore channels where they emerge on the sample support and the second gasconduit is sealed to another surface of the sample support with agas-tight seal, so as to surround the one or more channels where theyemerge on the other surface of the sample support. The one or more gastight seals may be accomplished by an o-ring elastomer seal, and/or therelevant surface of the sample support may itself comprise compressiblematerial.

Where the quantity of sample is located on the solid surface of thesample support in the form of a liquid drop, preferably an inlet of thesecond gas conduit (which may comprise a carrier tube) is placed incontact with a portion the solid surface of the sample support uponwhich the quantity of sample is located, and the second gas conduit atleast partially surrounds the quantity of sample and at least partiallysurrounds one or more channels, the channels extending from the firstside through to the second side of the solid surface, the quantity ofsample being located upon the second side of the solid surface. Morepreferably the inlet of the second gas conduit is in contact with andforms a gas tight seal with the solid surface upon which the quantity ofsample is located, and the second gas conduit at least partiallysurrounds the quantity of sample and at least partially surrounds one ormore channels, the channels extending from the first side through to thesecond side of the solid surface, the quantity of sample being locatedupon the second side of the solid surface. Alternatively, the samplesupport may comprise a protuberance such as a small rod, in which caseeither: a single gas conduit is used and the gas conduit at leastpartially surrounds the protuberance; or the first gas conduit or thesecond gas conduit at least partially surrounds the protuberance, and anoutlet of the first gas conduit is at least partially connected to aninlet of the second gas conduit.

Where the quantity of sample is located on the solid surface of a samplesupport within a containment vessel and the second surface of the samplesupport is inside the containment vessel and is the inside lower surfaceof the containment vessel, preferably the second gas conduit (which maycomprise a carrier tube) at least partially surrounds and morepreferably fully surrounds one or more channels where they emerge on thethird surface of the sample support, the channels extending from thefirst surface of the sample support through to a third surface of thesample support as described above. In another preferred embodiment, thechannels extend from one location on the third surface to anotherlocation on the third surface, as will be further described. Where thisthird surface of the sample support comprises a rim, the inlet of thesecond gas conduit preferably also abuts the rim, more preferably with agas-tight seal, so as to surround the one or more channels as theyemerge on the third surface. The gas tight seal may be accomplished byan o-ring elastomer seal, and/or the surface of the sample support mayitself comprise compressible material.

An alternative arrangement for supplying the stream of gas through a gasconduit comprises a first gas conduit coupled to the gas supply andcoupled to the sample support, and a second gas conduit being coupled tothe sample support and the inlet of the analysis device, wherein thefirst gas conduit supplies gas into a first set of one or more channelsin the sample support and the second gas conduit receives gas from asecond set of one or more channels in the sample support, the first setof one or more channels being in gaseous communication with the secondset of one or more channels. Preferably both the first set of one ormore channels and the second set of one or more channels are accessiblefrom the same surface of the sample support and most preferably thissurface is the third surface of the sample support as described above,in which case the acoustic transducer is not contained within the firstgas conduit. In this case, the gas conduit supplies the stream of gas inthe form of a gas curtain at least partially surrounding a volumeadjacent the sample support site so as to partially surround the dropletof sample as it leaves the surface of the quantity of sample on thesample support site. An example of such an embodiment is given below.

The gas conduit extending from the region of the sample to the analysisdevice may extend in a straight line (i.e. the axis of the gas conduitextends in a straight line), or it may extend so as to incorporate oneor more changes of direction (e.g. it may extend along a curved path).Preferably the path is such that the droplet of sample does not contactany solid surface along the transport path after leaving the quantity ofsample and before entering the analysis device, and depending upon thediameter of the gas conduit (amongst other conditions), this may limitthe minimum radius of curvature of any curved section, for example.Preferably the gas conduit extends axially a distance between 10 and 100mm from the region of the sample to the analysis device. In someembodiments the gas conduit may be longer than this, extending between100 and 1000 mm. Where an ejected droplet size is too large forefficient direct injection into the analysis device, a droplet modifiermay be incorporated into the transport path, as described below, inwhich case the second conduit or carrier tube may incorporate such adroplet modifier in the arrangement between the sample support and theinlet of the analysis device.

The gas conduit extending from the region of the sample to the analysisdevice may have different cross sectional shapes (the cross sectionbeing normal to the tube axis). Preferably the gas conduit cross sectionis substantially circular. Preferably the internal cross sectional areareduces somewhat (i.e. the conduit narrows in at least one dimension) asthe gas conduit extends away from the sample support, in order toincrease the flow velocity of the gas in a region above the surface ofthe quantity of liquid sample.

Preferably the gas stream enters the analysis device as it enters asample inlet. Preferably an outlet of the gas conduit is directlyconnected to the inlet of the analysis device. More preferably the gasconduit forms a single component with the inlet of the analysis deviceso that there are no discrete step changes in the gas flow resistancewhich may increase the risk of droplets contacting a solid surface.Where the outlet of the gas conduit is directly connected to the inletof the analysis device, preferably the internal cross sectional area ofthe inlet of the analysis device is larger than the internal crosssectional area of the outlet of the gas conduit. Preferably the dropletof sample entrained in the gas stream enters the analysis device andmaterial within the entrained droplet of sample is excited or ionizedwithin the analysis device without having come into contact with anysolid surface on its journey from the quantity of sample.

The analysis device is preferably one of: an Atomic AbsorptionSpectrometer, an Inductively Coupled Plasma Optical EmissionSpectrometer, an Inductively Coupled Plasma Mass Spectrometer, aMicrowave Induced Plasma Optical Emission Spectrometer, a MicrowaveInduced Plasma Mass Spectrometer, an Atomic Fluorescence Spectrometer, aLaser Enhanced Ionization Spectrometer. The invention is highly suitablefor application with either an Inductively Coupled Plasma OpticalEmission Spectrometer or an Inductively Coupled Plasma MassSpectrometer. Most preferably the analysis device is an InductivelyCoupled Plasma Optical Emission Spectrometer.

Alternatively, the analysis device may be a time-of-flight massspectrometer utilizing a desolvation membrane such as a Nafion™ tube,and an ionization device such as a corona discharge, a photo-ionizationsource, or a radioactive ionizing source such as ⁶³Ni foil, ²⁴¹Am ortritium (³H). The analysis device may also be an ion mobility analyser,utilizing a desolvation membrane such as a Nafion™ tube. Other types ofanalysis device suitable for use with the invention are envisaged.

The inlet of the analysis device preferably comprises the inlet to theinjector tube of a torch, where the analysis device utilizes a torch(such as in, for example, an ICP-OES or ICP-MS). Where the analysisdevice is an atomic absorption spectrometer the inlet of the analysisdevice comprises the inlet to the burner. Where the analysis device isan atomic fluorescence spectrometer, the inlet to the analysis devicecomprises an inlet to the optical cell.

The droplet may be of any size suitable for the analysis device.Preferably the droplet size lies in the range 0.1 to 10 μm in diameter.Droplets of this size are suitable for highly efficient direct injectioninto an inductively coupled plasma, for example. Alternatively thedroplet diameter may be 10 to 200 μm. Droplets of this size may beadvantageous where a higher sample flow rate is required and a limitedacoustic energy repetition rate is available.

Larger droplets may require a droplet modifier located between thequantity of sample and the analysis device and in the transport path ofthe droplet of sample as it is transported using the gas stream, thedroplet modifier being configured to remove solvent from the droplet.Preferably solvent is removed from the droplet by evaporation using aheated gas, an optical heater, convective heater, microwave heater, R.F.heater, or a broadband I.R. source, e.g., LED, laser, electricallyexcited filament; or a narrowband I.R. source e.g., LED or a laser.Accordingly, the droplet modifier preferably comprises one or more ofthe aforementioned means (supply of heated gas, an optical heater etc.).When using a narrowband source the source will preferably emit at awavelength that is matched to an absorbance frequency of the sample.

Preferably the acoustic energy is repeatedly applied to the quantity ofsample so as to produce a stream of droplets from one quantity of liquidsample for a period of time. Preferably the acoustic transducer iscontrolled by a computer.

In preferred embodiments the sample support comprises a well plate, eachwell having an internal capacity of between 5 μl and 2 ml. Preferablythe well plate contains a plurality of wells. Where the sample supportcomprises a plurality of sample support sites, such as containmentvessels, indentations, protuberances, or sites having undergone surfacetreatment such as etching or impregnation, preferably the relativepositions of the sample support and the acoustic transducer areperiodically changed so as to position a different quantity of sample inthe path of acoustic energy emitted by the acoustic transducer. Inpreferred embodiments the sample support is moved relative to theacoustic transducer so that acoustic energy may be sequentially appliedto some or all the sample support sites included in the sample support.Preferably the relative movement of the sample support and the acoustictransducer is accomplished using automated means and is controlled by acomputer. The gas conduit is preferably also moved relative to thesample support, preferably by automated means, so that the gas conduitmay deliver gas to and from different sample support sites. Both theacoustic transducer and the gas conduit are preferably moved indirections perpendicular to the sample support using linear actuators.Various such actuators are known in the art. Once the acoustictransducer and gas conduit have been moved away from the sample support,the sample support may be repositioned and the acoustic transducer andgas conduit may then be reapplied to the sample support so that samplemay be emitted from a new sample support site and transported in the gasstream to the analysis device. Where the sample support comprises anarray of sample support sites arranged in a circle, advantageously thesample support may simply be rotated in order to position a differentsample support site into the path of the acoustic transducer and in thepath of the gas conduit.

Identification of different sample support sites may be accomplished byknown means, such as barcodes or RFID recognition, so that differentsamples may be tracked and different types of sample supportarrangements may be identified.

Advantageously, the gas conduit, acoustic droplet generator, samplesupport plate and inlet of the analysis device may be contained withinan enclosure filled with inert gas such as argon, so that sampleslocated on the sample support are not exposed to ambient air.Alternatively, where samples are contained within vessels, each vesselmay be covered by a film of a polymer to protect the samples fromambient air, and during the process of locating the second gas conduitonto the sample support adjacent a sample support site the polymer filmseal may be broken to provide a path for emitted droplets from thesample support site.

Quantities of sample may be introduced onto or into the one or moresample support sites manually or by automated means. Quantities ofdifferent samples may be located on different sample support sites.Where there are multiple sample support sites, the quantities of sampleor samples are preferably introduced onto or into multiple samplesupport sites simultaneously by automated means. Automated means includepumps as are known in the art, or by any other means.

Two different liquids may be introduced to an analysis device forsimultaneous analysis using a method comprising the steps of: using afirst droplet-on-demand generator to provide a first stream of dropletsof a first liquid; using a second droplet-on-demand generator to providea second stream of droplets of a second liquid and combining the firstand second streams of droplets before they enter the analysis device.The method may be performed using a sample introduction system for ananalysis device comprising a first droplet-on-demand generator suitablefor generating a stream of droplets from a first liquid; a seconddroplet-on-demand generator suitable for generating a stream of dropletsfrom a second liquid; a gas supply arranged to supply a first stream ofgas to entrain droplets generated from the first liquid; a gas supplyarranged to supply a second stream of gas to entrain droplets generatedfrom the second liquid; and a gas conduit upstream of an inlet of theanalysis device arranged to combine the first and second streams of gasbefore they enter the analysis device.

A droplet-on-demand droplet generator is a type of droplet generator inwhich the droplet generation apparatus enables a single droplet to beejected in response to a control signal. The invention may be applied tovarious known and as-yet unknown droplet-on-demand generators.Preferably the droplet-on-demand generator comprises one of apiezo-actuated droplet generator, a thermal inkjet device, amonodisperse dried microparticulate injector, an acoustic transducer(e.g. configured in a sample introduction system according to thefurther aspect independent of the invention described herein).

Where there are multiple sample support sites, preferably some of thesample support sites may be sites for the location of quantities ofdiluent and some may be sites for the location of quantities of one ormore standards. The provision of more than one droplet-on-demandgenerator, which preferably comprises an acoustic transducer, may thenbe used for substantially simultaneous emission of a stream of dropletsof sample from a first site, and a stream of droplets of a diluentand/or one or more standards from one or more other sites. Preferablythe first and second streams of droplets are combined in a gas streamand the gas stream transports the droplets to the inlet of the analysisdevice. Preferably each site upon the sample support is provided with agas stream, and the gas streams are combined prior to them reaching theanalysis device, thereby mixing the streams of droplets prior toreaching the analysis device, the streams of droplets consisting ofdifferent constituents from the different sites, the differentconstituents being delivered to the analysis device simultaneously.Preferably the gas stream or gas streams comprise inert gas and morepreferably substantially only inert gas. Preferably the inert gascomprises argon. Advantageously the effective mixing occurs whilst thedroplets are in flight and are not in contact with any surfaces. Hence,preferably a plurality of droplets is created substantiallysimultaneously from a plurality of quantities of liquid each located ona solid surface and wherein at least one quantity of liquid comprisessample and one quantity of liquid comprises diluent and/or a standard.The droplets of sample are transported into the analysis device using agas stream, and the gas stream comprises a first gas stream, and asecond gas stream is combined with the first gas stream, the second gasstream containing droplets of diluent or droplets of a standard. Wherethe sample is dispensed using a droplet-on-demand generator comprisingan acoustic transducer, the sample advantageously does not come intocontact with any solid surface other than the surface of the samplesupport and hence there is no wash-out required between the analysis ofdifferent samples, as the different samples are located upon differentsample support sites. In this case, the second droplet-on-demandgenerator may be of any type, as it is only dispensing a single solutioncontaining diluent and/or standard to be combined with differentsamples.

In cases where a low droplet admission rate into the analysis device isrequired, the droplet stream may be diluted by the addition of anadditional gas downstream of the sample support. Dilution is in thiscase a reduction in the droplet density in the gas stream entering theanalysis device, and it is achieved by adding an additional gas streaminto the gas stream in which the droplets are entrained. The additionalgas may be of the same or similar composition to the gas stream in whichthe droplets are entrained, or it may be a different gas. The additionalgas may also serve to increase the gas flow rate into the analyticaldevice where that device requires a higher gas flow rate than isdesirable to entrain the droplets. Hence there is a method ofintroducing liquid sample into an analysis device as previouslydescribed wherein the gas stream comprises a first gas stream, and asecond gas stream is combined with the first gas stream upstream of theanalysis device.

Advantageously, the present invention provides for supplyingacoustically emitted droplets to an analysis device by entraining thedroplets in a gas stream. In prior art systems, acoustic dropletgenerators have been used to emit droplets from a quantity of sample andto deposit them onto another surface in relatively close proximity tothe acoustic transducer. In the present invention the gas streamadvantageously transports the droplets into the analysis devicedirectly. Preferably the droplets are transported into the analysisdevice without having come into contact with any surface once they leavethe surface of the quantity of liquid sample. The use of an acousticdroplet generator with an analysis device enables droplets to besupplied to the analysis device without the use of tubing to transfersample-containing liquid from a storage vessel to the droplet generatorand wherein the droplet generator itself does not present exposedsurfaces to the sample-containing liquid. There is therefore norequirement to wash out tubing or surfaces of the droplet generator inbetween the uptake of different samples, and throughput of samples tothe analysis device is greatly increased.

Other advantages provided include the mixing of sample with diluentand/or standards within the gas flow entering the inlet of the analysisdevice, without the requirement for any mixing vessel, the surfaces ofwhich would otherwise require cleaning before another sample could beadmitted. Mixing occurs within the gas stream without furtherintervention, and so no additional mixing devices are required, reducingcomplexity.

DESCRIPTION OF THE DRAWINGS

FIG. 1 is a schematic diagram of a prior art droplet ejection systemutilizing an acoustic droplet ejector.

FIG. 2 is a schematic diagram of a prior art sample introduction systemfor sample analysis using an analysis device.

FIGS. 3A-3C are schematic diagrams of embodiments of the presentinvention, FIG. 3A is a schematic diagram of the top-view of a wellplate. FIG. 3B is a schematic cross sectional diagram of the well plateof FIG. 3A in the section marked A-A. FIG. 3C is the schematic crosssectional diagram of the well plate of FIG. 3B with additionalcomponents shown.

FIG. 4 is a schematic cross-sectional diagram of another embodiment ofthe present invention.

FIG. 5 is a schematic cross-sectional diagram of yet another embodimentof the invention.

DETAILED DESCRIPTION

FIG. 1 is a schematic diagram of a prior art droplet ejection systemutilizing an acoustic droplet ejector. Liquids to be dispensed, 10, arecontained within an array of sample vessels, 20, in this case awell-plate. An acoustic transducer and lens system, 30, provides pulsedacoustic energy, 40, which travels from the acoustic transducer, 32, andthrough the incorporated lens system, 34, before being emitted to passthrough the well-plate, 20, and into one of the vessels, 22. The lenssystem, 34, incorporated into the transducer and lens system 30 isarranged to focus the acoustic pulse on the surface region, 12, of theliquid within the vessel, 22. Upon arrival at the surface region, 12,the acoustic energy, 40, disrupts the surface of the liquid so as toeject a droplet, 14, of the liquid, 10. The droplet, 14 (not to scale),leaves the surface region, 12, and travels upward, approximatelyorthogonally away from the surface region 12, and is deposited onreceiving plate 50, within one of the wells therein. By this meansliquids may be transferred droplet by droplet from a sample vessel, 22to a receiving plate, 50. The relative positions of the acoustictransducer and lens system, 30, the array of sample vessels, 20, and thereceiving plate, 50, may be varied, so that sample liquids withindifferent vessels in the array 20 may receive focused acoustic energyand the emitted droplets may be collected at different places uponreceiving plate 50. Preferably the relative positions are determinedusing automated means. Different liquid levels within different samplevessels in array 20 may require variation of the focusing of the lenssystem 34 in order to ensure acoustic energy is focused in the surfaceregions of the respective liquids. Methods have been devised to measurethe liquid level within such vessels using acoustic energy reflectedfrom the liquid surface and such information can be used to continuallyvary the focusing properties of the lens system 34 in an automatedmanner.

FIG. 2 is a schematic diagram of a prior art sample introduction systemfor sample analysis using an inductively coupled plasma massspectrometer (ICP-MS) as the analysis device. FIG. 2 shows a nebulizer,60, having sample inlet tube 62 and gas inlet tube 64. Typicallynebuilser 60 is made of glass. In use, a stream of liquid sample (notshown) is supplied into inlet tube 62, whilst an inert gas, usuallyargon, is supplied into gas inlet tube 64. The inert gas has sufficientflow velocity as it exits from the tip of the nebulizer 66 to cause alocal drop in pressure which acts to draw liquid sample from thenarrowed sample inlet tube 68 and to break the liquid emerging from tube68 into droplets 69. A large range of droplets sizes is produced by suchnebulizers. The gas flow from the nebulizer 60 emerges into spraychamber 70, which in this example is an impact-bead spray chamber havingimpact bead 72. Spray chamber 70 is typically made of glass or an inertpolymer. The sample droplets 69 are entrained in the gas stream and manydroplets are caused to strike impact bead 72, whilst a proportion flowaround impact bead 72. Droplets which strike impact bead 72 arepredominantly the larger droplets, and by this means impact bead 72serves to filter out larger droplets, the liquid within such dropletsflowing down impact bead 72 and flowing to waste through waste outlet74. As already noted, with pneumatic nebuilsers of the type described,only 1-2% of the droplets produced are of a size useful for analysis.Smaller droplets which flow around impact bead 72 are carried by the gasstream to outlet 76 and enter the inlet of torch 80. Torch 80 comprisesinjector tube 82, auxiliary tube 84 and outer tube 86. Typically torch80 is made of quartz glass or ceramic elements. The gas flow enteringinjector tube 82 is known as an injection gas. Additional gas issupplied to auxiliary tube 84 via inlet 85, and this gas flow is knownas auxiliary gas. A further gas flow is supplied to outer tube 86 viainlet 87, and this gas flow is known as the cool gas, as it ispredominantly used to introduce a barrier of gas along the insidesurface of outer tube 86. ICP coil 90 is used to couple RF power(typically, at 27 MHz) into a plasma formed within outer tube 86 in theregion 88 (plasma is not shown). Droplets entering the inlet of torch 80via injector tube 82 are transported in the injector gas into the axialregion of the plasma 91 whereupon they desolvate and atomise and aproportion of the atoms liberated are ionized. Sample products passingthrough the plasma enter sample cone 92 through orifice 94, and passinto the inlet system of the mass spectrometer (not shown).

The nebulizer 60, spray chamber 70 and torch 80 of FIG. 2 mayalternatively be used with an ICP-OES analysis device. Similar torcharrangements are used in MIP spectrometry; AA and AFS use somewhatdifferently designed torches.

FIGS. 3A-3C are schematic diagrams of embodiments of the presentinvention. FIG. 3A is a schematic diagram of the top-view of a wellplate. FIG. 3B is a schematic cross sectional diagram of the well plateof FIG. 3A in the section marked A-A. FIG. 3C is the schematic crosssectional diagram of the well plate of FIG. 3B with additionalcomponents shown. Well plate 300 is depicted in FIGS. 3A-3C, comprisingthree wells, 301, 302, 303, each well comprising a sample support site;hence there are depicted three sample support sites and the well plate300 contains a plurality of wells. Well 302 comprises side wall 304, andwell 302 has inside lower surface 306 upon which a quantity of liquidsample 310 is located (quantity of sample 310 cannot be seen in FIG.3A). The quantity of liquid sample 310 partially fills well 302 andcompletely covers the inside lower surface 306; hence a solid surface ofa sample support comprises inside lower surface 306 of well 302 in thisexample (i.e. the inside lower surface 306 is a sample support site).

Well plate 300 further comprises channels 320 which partially surroundwells 301, 302, 303. With reference to well 302, channels 320 extendfrom a first surface 307 and within one or more side walls 304 of well302 to a third surface 309, surface 309 being a greater distance fromthe first surface 307 than is the quantity of sample 310, the thirdsurface 309 forming the rim of well 302. First surface 307 may includeportions of curved surface, and may include flat surfaces with changesof direction as shown in FIG. 3B. Channels 320 do not completelysurround the rim of well 302 as supporting ribs 322 are provided (shownin FIG. 3A), attaching the inner wall portion 323 of well 302 to anouter wall portion 324 of well 302. In this example the supporting ribs322 extend from third surface 309 to first surface 307, providing arigid attachment between portions 323 and 324. In other embodimentssupporting ribs may only extend part of the way from third surface 309towards first surface 307 and there may be more supporting ribs toachieve a similar degree of rigidity.

FIG. 3C shows acoustic transducer 350 which is arranged so that, in use,acoustic energy is emitted towards the first surface 307 of the samplesupport of well 302 and the quantity of liquid sample 310 is locatedupon a second surface 308 of the sample support. In this example secondsurface 308 of the sample support is the same surface as inside lowersurface 306 and surface 308 forms the solid surface upon which thequantity of sample 310 is located. A portion of the first surface 307and the second surface 308 of the sample support are substantiallyparallel to one another. Acoustic energy is emitted from acoustictransducer 350 towards the solid surface upon which the quantity ofsample 310 is located, the acoustic energy passing through the firstsurface 307 of the sample support and out of the second surface 308 ofthe sample support.

A gas supply (not shown) is arranged to supply a stream of gas 335 to afirst gas conduit 330, the first gas conduit 330 arranged between thegas supply and the sample support, A second gas conduit 340 is arrangedbetween the sample support (well 302) and an inlet of an analysis device(not shown). Hence in this example the gas conduit arranged between thegas supply and the sample support and between the sample support and aninlet of the analysis device comprises a first gas conduit 330 and asecond gas conduit 340. The inlet of the second gas conduit 340 abutsthe rim of well 302 and surrounds channels 320 as they emerge on thethird surface 309. The stream of gas 335 travels along gas first gasconduit 330 to the first surface 307 of the sample support and flowsinto and through channels 320, emerging from channels 320 into secondgas conduit 340 whereupon the gas stream travels to the inlet of theanalysis device. Hence the gas stream is supplied so as to form a gascurtain which at least partially surrounds the quantity of sample 310whilst the gas travels within channels 320 formed within side walls 304of the well 302. The curtain of gas is primarily directed normal to andaway from the side of the solid surface 308 upon which the quantity ofsample 310 is located. As shown in FIG. 3C the acoustic transducer 350is located within the first gas conduit 330, along with acoustictransducer drive electronics 355 within a case 356. Electricalconnections to acoustic transducer drive electronics 355 are not shownin the figure, but pass through the wall of first gas conduit 330 to acontroller which comprises a computer (also not shown). The gas streampasses around case 356 which contains acoustic transducer driveelectronics 355 and acoustic transducer 350, within an annular channel331.

Acoustic energy is focused upon the surface region 312 of liquid sample310 (shown in FIG. 3C). The acoustic energy is focused using a lenssystem (not shown) which is incorporated with the transducer 350, thelens system being arranged to focus an acoustic pulse emitted bytransducer 350 onto the surface region 312 of the liquid sample 310within the well 302, the acoustic pulse passing through the lowersurface 306 of well 302. Upon arrival at the surface region 312, theacoustic energy (not shown) disrupts the surface of the liquid so as toeject a droplet, 314, of the liquid sample 310 (droplet 314 is not shownto scale). The droplet, 314, leaves the surface region, 312, and travelsupward, approximately orthogonally away from the surface of the liquidsample 310 and passes into the second gas conduit 340, whereupon thedroplet becomes entrained in the gas stream flowing in the second gasconduit 340 (as described above) and the droplet of sample istransported into the analysis device using the gas stream. The crosssectional shape of the second gas conduit 340 is substantially circular.The internal cross sectional area of the second gas conduit 340 reducessomewhat (i.e. the tube narrows) as the second gas conduit extends awayfrom the sample support, in order to increase the flow velocity of thegas in a region above the surface of the quantity of liquid sample 310.

The first gas conduit 330 is sealed to first surface 307 of the samplesupport with a gas-tight seal using elastomer 332 and the second gasconduit 340 is sealed to third surface 309 of the sample support with agas-tight seal using elastomer 342. The second gas conduit 340 serves toconstrain the gas stream as it travels from the sample support to theanalysis device, and thereby constrain the transport path of the ejecteddroplet. The second gas conduit extends 75 mm from the sample support tothe inlet of an ICP-OES analysis device and contains no abrupt changesof direction so that the droplet of sample does not contact any solidsurface along the transport path after leaving the quantity of sampleand before entering the analysis device. In this example the dropletdiameter is 5 μm and the droplet is highly suitable for direct injectioninto the inlet of the torch of the ICP-OES spectrometer, whereupon itmay be desolvated, atomized and excited with high efficiency.

In the embodiments of FIGS. 3A-3C, the wells 301, 302, 303 have internalcapacity of 500 ul and the well plate 300 is formed from polypropylene.The gas supply comprises argon gas, the gas flow rate being 0.5 l·min⁻¹at a pressure of 1.5-1.8 atm, the gas temperature being 20-25 degrees C.The average gas velocity in the second gas conduit is 1.2-1.5 m·s⁻¹.These working parameters are suitable for aqueous samples such asdrinking water for analysis in an ICP-OES analysis device.

The acoustic transducer 350 is controlled so as to repeatedly emitpulses of acoustic radiation of a first magnitude of acoustic energytowards the surface region 312 of the quantity of liquid sample 310,thereby repeatedly emitting droplets for entrainment in the gas stream.Periodically during this process, and before the first pulse of acousticradiation of a first magnitude of acoustic energy is applied to a freshquantity of liquid sample, a pulse of a second magnitude of acousticenergy is radiated, the second magnitude being lower than the firstmagnitude. This second magnitude pulse is used to determine the distancebetween the acoustic transducer 350 and the surface region 312 of thequantity of sample 310. This is achieved as transducer 350 alsocomprises a detector for detecting reflected acoustic energy. Bymeasuring the time period between the emitted pulse of acoustic energyand the detection of the reflected pulse of acoustic energy theeffective path length between the transducer 350 and the surface region312 of the quantity of liquid sample 310 may be determined, and thisinformation is used to adjust parameters controlling the lens whichfocuses the acoustic radiation of a first magnitude which issubsequently applied. This process is periodically utilized during asequence of pulses of acoustic radiation of a first magnitude ofacoustic energy so that the location of the surface region 312 of thediminishing quantity of liquid sample 310 may be correctly determined.

Quantities of different samples are located within wells 310, 302 and303. The relative positions of the sample support (the well plate 300)and the acoustic transducer 350 are periodically changed so as toposition a different quantity of sample in the path of acoustic energyemitted by the acoustic transducer 350. The sample support is movedrelative to the acoustic transducer so that acoustic energy may besequentially applied to each of wells 301, 302 and 303 in well plate300. By moving the sample support and keeping the transducer 350 at thesame position relative to the inlet of the analysis device, the path ofsecond gas conduit 340 remains fixed and it can be ensured that thedroplets do not come in contact with any solid surface between leavingthe quantity of sample and entering the analysis device. The relativemovement of the sample support 300 and the acoustic transducer 350 isaccomplished using automated means and is controlled by a computer. Thefirst and second gas conduits 330,340 are moved by linear actuators (notshown) orthogonally to first surface 307 and third surface 309respectively to disengage from the well plate 300, enabling well plate300 to be moved so that first and second gas conduits 330, 340 may bere-engaged with well plate 300 aligned with a different well. Acoustictransducer 350, acoustic transducer electronics 355 and case 356 beingattached to first gas conduit 330 move with first gas conduit 330.

A gas stream is supplied at a first flow rate whilst transporting thedroplet of sample 314 from the quantity of liquid sample 310 to theanalysis device, and a gas stream is supplied at a second flow rate whennot transporting a droplet of sample and immediately prior to applyingthe acoustic energy to the quantity of sample, the second flow ratebeing greater than the first flow rate. The application of the secondgas stream advantageously purges the volume in the region around thequantity of sample of residual gases prior to droplet ejection, and thisapplication of the second gas stream is performed immediately afterpositioning a different quantity of sample in the path of acousticenergy emitted by the acoustic transducer 350 so that residualatmospheric gases included during the positioning process are notcarried into the analysis device at the same time as droplets of sample.

FIG. 4 is a schematic cross-sectional diagram of a further embodiment ofthe present invention. This embodiment shares some of the features ofthe previous embodiment described in relation to FIG. 3 and likecomponents have the same identifiers. Well plate 400 is depicted in FIG.4, comprising three wells 401, 402, 403. Well 402 comprises side wall404, and well 402 has inside lower surface 406 upon which a quantity ofliquid sample 410 is located. The quantity of liquid sample 410partially fills well 402 and completely covers the inside lower surface406; hence a solid surface of a sample support comprises inside lowersurface 406 of well 402 in this example.

Well plate 400 further comprises channels 420, and channels 421 whichconnect within the well plate to channels 420. Channels 420 and channels421 are accessible from only a single surface 409 of well plate 400, thesurface being previously described as the third surface. Surface 409comprises the rim of well 402. Channels 420 and 421 do not completelysurround the rim of well 402, supporting ribs being provided (but notshown) in a similar manner to ribs 322 in FIG. 3, however both channels420 and 421 almost completely surround the rim of well 402.

Acoustic transducer 350 is arranged in a similar manner to thatdescribed in relation to FIG. 3, so that, in use, acoustic energy isemitted towards first surface 407 of the sample support of well 402, thequantity of liquid sample 410 being located upon second surface 408 ofthe sample support. However in the embodiment of FIG. 4 the acoustictransducer 350, acoustic transducer drive electronics 355 and case 356are not located within a first gas conduit, but are instead unenclosed.A portion of the first surface 407 and the second surface 408 of thesample support are substantially parallel to one another. Acousticenergy is emitted from acoustic transducer 350 towards the solid surfaceupon which the quantity of sample 410 is located, the acoustic energypassing through the first surface 407 of the sample support and out ofthe second surface 408 of the sample support. Acoustic energy is focusedas described in relation to FIG. 3 and the pulse of focused acousticenergy (not shown) ejects a droplet 414 of the liquid sample fromsurface region 412 of the liquid sample 410.

In this embodiment a gas supply (not shown) is arranged to supply astream of gas 335 to a first gas conduit 430, the first gas conduit 430arranged between the gas supply and the sample support. The stream ofgas 335 passes into channels 421 and then into channels 420, emergingfrom surface 409 into a region above the surface of the liquid sample410, the region being within a second gas conduit 440 whereupon the gasstream travels to the inlet of the analysis device. Second gas conduit440 is arranged between the sample support and an inlet of the analysisdevice (not shown). Hence the gas stream is supplied so as to form a gascurtain at least partially surrounding a volume adjacent the samplesupport site so as to partially surround the droplet of sample as itleaves the surface of the quantity of sample on the sample support site.The curtain of gas is primarily directed normal to and away from theside of the solid surface 408 upon which the quantity of sample 410 islocated as it travels in channels 420 and in the second gas conduit 440in the region immediately above the surface of the liquid sample 410.

The droplet, 414, leaves the surface region, 412, and travels upward,approximately orthogonally away from the surface of the liquid sample410 and passes into the second gas conduit 440, whereupon the dropletbecomes entrained in the gas stream flowing in the second gas conduit440 and the droplet of sample is transported into the analysis deviceusing the gas stream. The cross sectional shape of the second gasconduit 440 is substantially circular. The internal cross sectional areaof the second gas conduit 440 reduces somewhat (i.e. the tube narrows)as the second gas conduit extends away from the sample support, in orderto increase the flow velocity of the gas in a region above the surfaceof the quantity of liquid sample 410.

The first gas conduit 430 is sealed to third surface 409 of the samplesupport with a gas-tight seal using elastomer 432 and the second gasconduit 440 is sealed to third surface 409 of the sample support with agas-tight seal using elastomer 442. The second gas conduit 440 serves toconstrain the gas stream as it travels from the sample support to theanalysis device, and thereby constrain the transport path of the ejecteddroplet. The second gas conduit extends 55 mm from the sample support tothe inlet of an ICP-MS analysis device and contains no abrupt changes ofdirection so that the droplet of sample does not contact any solidsurface along the transport path after leaving the quantity of sampleand before entering the analysis device. In this example the dropletdiameter is 5 μm and the droplet is highly suitable for direct injectioninto the inlet of the torch of the ICP-MS spectrometer, whereupon it maybe desolvated, atomized and ionised with high efficiency.

In the embodiment of FIG. 4, the wells 401, 402, 403 have internalcapacity of 500 μl and the well plate 400 is formed from polypropylene.The gas supply comprises argon gas, the gas flow rate being 0.7 l·min⁻¹at a pressure of 1.5 atm, the gas temperature being 20 degrees C. Theaverage gas velocity in the second gas conduit is 1.5 m·s⁻¹. Theseworking parameters are suitable for aqueous samples such as drinkingwater for analysis in an ICP-MS analysis device.

The operation of the acoustic transducer is controlled in a mannersimilar to that described in relation to the embodiment of FIG. 3.Quantities of different samples are located in the different wells ofwell plate 400 and the relative motion of the acoustic transducer 350and sample support plate 400 enables different samples to be dispensedfrom well plate 400. Acoustic transducer 350, acoustic transducerelectronics 355 and case 356 are moved in this embodiment using a linearactuator (not shown), which has movement in a direction orthogonal tofirst surface 407. Gas conduits 430 and 440 are advantageously moved asone in the embodiment of FIG. 4, by a second linear actuator (not shown)which has movement in a direction orthogonal to third surface 409. Bythis means acoustic transducer 350, acoustic transducer electronics 355and case 356 are disengaged from well plate 400, and first and secondgas conduits 430, 440 are also disengaged from well plate 400 enabling adifferent well in well plate 400 to then be positioned so that acoustictransducer 350, acoustic transducer electronics 355, case 356 and gasconduits 430, 440 may engage onto the different well, and a differentsample may be dispensed. Well plate 400, first and second gas conduits430, 440, the inlet to the analysis device and case 356 containingacoustic transducer 350 and acoustic transducer electronics 355 are allmaintained in a protective argon atmosphere so that during the processof positioning a different well for the dispensing of a differentsample, contaminant gases are substantially excluded from all the wellsand the gas conduits.

FIG. 5 is a schematic cross-sectional diagram of yet another embodimentof the invention. FIG. 5 depicts a well plate 500, comprising wells 501,502, 503, 504, 505, each well being partially filled with a fluid. Well502 is partially filled with liquid sample 510 and well 505 is partiallyfilled with a solution containing a liquid standard, 511. A firstacoustic transducer system 550 is arranged to deliver multiple pulses ofacoustic energy focused on the surface region of liquid 510 so as toeject a stream of droplets of liquid sample from the surface, and asecond acoustic transducer system 551 is arranged to deliver multiplepulses of acoustic energy focused on the surface region of liquid 511,so as to eject a stream droplets of liquid standard from the surface.Coupled to well 502 is gas conduit 530 for providing a gas stream 535,and also coupled to well 502 is gas conduit 540 for guiding gas 535 awayfrom the well 502. Coupled to well 505 is gas conduit 531 for providinga gas stream 536, and also coupled to well 505 is gas conduit 541 forguiding gas 536 away from the well 505. Channels are formed within wellplate 500 connecting gas conduit 530 to gas conduit 540, and connectinggas conduit 531 to gas conduit 541, in a similar way to the arrangementdescribed in relation to the embodiment of FIG. 4. Droplets emitted fromliquid sample 510 are entrained in gas stream 535 within gas conduit540. Droplets emitted from liquid standard 511 are entrained in gasstream 536 within gas conduit 541. Gas conduits 540 and 541 areconnected together at 542 and gas streams 535 and 536 are combined toform gas stream 537 which flows through gas conduit 543 which isconnected to an inlet of an analysis device (not shown). Hence thestream of droplets of sample is combined with the stream of droplets ofstandard before they enter the analysis device. Gas 535 and gas 536 arehigh purity argon, although it will be appreciated that in otherembodiments another suitable gas or gases may be used. Gas conduits 540,541, 543 are arranged so that there are no abrupt changes of directionfor the gas flowing within the conduits, and this ensures that nodroplets contact any solid surface after leaving the well plate andbefore entering the analysis device.

As used herein, including in the claims, unless the context indicatesotherwise, singular forms of the terms herein are to be construed asincluding the plural form and vice versa. For instance, unless thecontext indicates otherwise, a singular reference herein including inthe claims, such as “a” or “an” means “one or more”.

Throughout the description and claims of this specification, the words“comprise”, “including”, “having” and “contain” and variations of thewords, for example “comprising” and “comprises” etc, mean “including butnot limited to”, and are not intended to (and do not) exclude othercomponents.

It will be appreciated that variations to the foregoing embodiments ofthe invention can be made while still falling within the scope of theinvention. Each feature disclosed in this specification, unless statedotherwise, may be replaced by alternative features serving the same,equivalent or similar purpose. Thus, unless stated otherwise, eachfeature disclosed is one example only of a generic series of equivalentor similar features.

The use of any and all examples, or exemplary language (“for instance”,“such as”, “for example” and like language) provided herein, is intendedmerely to better illustrate the invention and does not indicate alimitation on the scope of the invention unless otherwise claimed. Nolanguage in the specification should be construed as indicating anynon-claimed element as essential to the practice of the invention.

1. A method of introducing liquid sample into an analysis devicecomprising the steps of: applying acoustic energy to a quantity ofliquid sample located on a solid surface of a sample support so as toeject a droplet of sample from the quantity of sample; entraining thedroplet of sample in a gas stream; and transporting the droplet ofsample into the analysis device using the gas stream.
 2. The method ofclaim 1 wherein the droplet of sample does not contact any solid surfaceafter leaving the quantity of sample and before entering the analysisdevice.
 3. The method of claim 1 wherein the gas stream enters theanalysis device as it enters a sample inlet.
 4. The method of claim 1wherein the droplet of sample entrained in the gas stream enters theanalysis device and sample material within the entrained droplet ofsample is excited or ionized within the analysis device without havingcome into contact with any solid surface on its journey from thequantity of sample.
 5. The method of claim 1 wherein the quantity ofsample is located on the solid surface within a well plate.
 6. Themethod of claim 1 wherein the quantity of sample is located on the solidsurface in the form of a liquid drop.
 7. The method of claim 1 whereinthe solid surface comprises an inert material.
 8. The method of claim 1wherein the acoustic energy is applied to the quantity of sample throughthe solid surface.
 9. The method of claim 1 wherein the gas streamcomprises inert gas.
 10. The method of claim 1 wherein the analysisdevice is one of: an Atomic Absorption Spectrometer, an InductivelyCoupled Plasma Optical Emission Spectrometer, an Inductively CoupledPlasma Mass Spectrometer, a Microwave Plasma Optical EmissionSpectrometer, a Microwave Plasma Mass Spectrometer, an AtomicFluorescence Spectrometer, and a Laser Enhanced Ionization Spectrometer.11. The method of claim 1 wherein the droplet diameter lies in the rangeof 0.1-10 μm.
 12. The method of claim 1 wherein the droplet diameterlies in the range of 10-200 μm.
 13. The method of claim 1 wherein thegas stream is supplied so as to form a gas curtain which at leastpartially surrounds the droplet of sample as it leaves the quantity ofsample.
 14. The method of claim 1 wherein the gas stream is supplied ata first flow rate while transporting the droplet of sample, and the gasstream is supplied at a second flow rate when not transporting a dropletof sample and immediately prior to applying the acoustic energy to thequantity of sample, the second flow rate being greater than the firstflow rate.
 15. The method of claim 1 wherein a flow of inert gas isdirected at the quantity of sample on the solid surface immediatelyprior to applying the acoustic energy to the quantity of sample.
 16. Themethod of claim 1 wherein a plurality of droplets is createdsubstantially simultaneously from a plurality of quantities of liquideach located on a solid surface and wherein at least one quantity ofliquid comprises sample and one quantity of liquid comprises diluent ora standard.
 17. The method of claim 1 wherein the gas stream comprises afirst gas stream, and a second gas stream is combined with the first gasstream, the second gas stream containing droplets of diluent or dropletsof a standard.
 18. The method of claim 1 wherein a droplet modifier islocated between the quantity of sample and the analysis device and inthe path of the droplet of sample as it is transported using the gasstream, the droplet modifier being configured to remove solvent from thedroplet.
 19. The method of claim 1 wherein acoustic energy is repeatedlyapplied to the quantity of sample so as to produce a stream of droplets.20. The method of claim 1 wherein the acoustic energy is applied byemitting acoustic energy from a transducer and the solid surface isperiodically moved relative to the transducer so as to position adifferent quantity of sample in the path of the acoustic energy emittedby the transducer.
 21. The method of claim 20 further comprising thestep of piercing a polymer film seal attached to the sample supportimmediately after positioning a different quantity of sample in the pathof the acoustic energy.
 22. A sample introduction apparatus for ananalysis device comprising: a solid surface of a sample support suitablefor locating a quantity of liquid sample; an acoustic transducerarranged so that, in use, acoustic energy is emitted towards the solidsurface; a gas supply arranged to supply a stream of gas; and a gasconduit arranged between the gas supply and the sample support andbetween the sample support and an inlet of the analysis device.
 23. Theapparatus of claim 22 wherein the gas conduit comprises a first gasconduit arranged between the gas supply and the sample support and asecond gas conduit arranged between the sample support and an inlet ofthe analysis device.
 24. The apparatus of claim 23 wherein, the samplesupport, the second gas conduit, the inlet of the analysis device and atleast part of the first gas conduit are contained within an enclosurefilled with an inert gas.
 25. The apparatus of claim 22 wherein thesolid surface of the sample support comprises a sample support sitesuitable for locating a quantity of liquid sample, the sample supportsite comprising one or more of an indentation, a protuberance, or a sitehaving undergone surface treatment, and the sample support site ispartially or fully contained within the gas conduit.
 26. The apparatusof claim 22 wherein the sample support comprises an array of containmentvessels.
 27. The apparatus of claim 26 wherein multiple containmentvessels in the array of containment vessels contain quantities of liquidsample and sheets of polymer film seal the quantities of liquid samplewithin the containment vessels.
 28. The apparatus of claim 22 whereinthe sample support comprises one or more sample support sites composedof inert material.
 29. The apparatus of claim 22 wherein the stream ofgas is arranged to pass through a portion of the sample support in oneor more channels, the channels extending through a portion of the samplesupport.
 30. The apparatus of claim 29 wherein the sample support siteis an inside surface of a containment vessel and the channels extendwithin one or more side walls of the containment vessel.
 31. Theapparatus of claim 22 wherein the solid surface of the sample supportcomprises a sample support site suitable for locating a quantity ofliquid sample and the gas conduit is arranged to supply the stream ofgas in the form of a gas curtain at least partially surrounding a volumeadjacent the sample support site.
 32. The apparatus of claim 31 whereinthe gas conduit comprises a first gas conduit arranged to supply thestream of gas in the form of a gas curtain at least partiallysurrounding a volume adjacent the sample support site by passing itthrough one or more channels, the channels extending through a portionof the sample support.
 33. The apparatus of claim 32 wherein the gasconduit comprises a second gas conduit arranged to receive the gasemerging from the one or more channels and transport it to an inlet ofthe analysis device.
 34. The apparatus of claim 23 wherein the secondgas conduit extends axially a distance between 10 and 100 mm from theregion of the sample to the analysis device.
 35. The apparatus of claim23 wherein the second gas conduit has an internal cross sectional areawhich reduces as the second gas conduit extends away from the samplesupport.
 36. The apparatus of claim 22 further comprising a dropletmodifier located between the between the sample support and an inlet ofthe analysis device, the droplet modifier being configured to removesolvent from droplets of liquid which pass through it.
 37. The apparatusof claim 22 further comprising a controller and a mechanism for movingthe relative position of the sample support and the acoustic transducer.38. The apparatus of claim 22 wherein the analysis device is one of: anAtomic Absorption Spectrometer, an Inductively Coupled Plasma OpticalEmission Spectrometer, an Inductively Coupled Plasma Mass Spectrometer,a Microwave Plasma Optical Emission Spectrometer, a Microwave PlasmaMass Spectrometer, an Atomic Fluorescence Spectrometer, and a LaserEnhanced Ionization Spectrometer.